Four cases of audio-vestibular disorders related to immunisation with SARS-CoV-2 mRNA vaccines.

OBJECTIVE: To gain medical insight into the clinical course and safety of otolaryngologic disorders following immunisation with severe acute respiratory coronavirus (SARS-CoV-2) mRNA-based vaccines. DESIGN: Case description. STUDY SAMPLE: We report four cases of transient audio-vestibular symptoms, which occurred shortly after inoculation of two BNT162b2 (Pfizer-BioNTech®) and mRNA-1273 (Moderna®) vaccines. RESULTS: Hearing loss was unilateral in all cases and recovered at least partially: it was associated with persistent gait instability in two cases, after 1 and 7 months. Trigger mechanisms underpinning audio-vestibular impairment remain uncertain. Immune tolerance mechanisms with off-target innate activation of T-lymphocytes may be involved in vestibulocochlear nerve disorders, as for other cranial nerves involvement. CONCLUSIONS: The occurrence of audio-vestibular manifestations following mRNA-based vaccines needs ENT monitoring to support their causality in such rare vaccine-related adverse events. Audio-vestibular disorders appeared of transitory nature, including hearing loss, and should not deter further efforts in large-scale vaccination campaigns against SARS-CoV-2.

Cardiovascular therapy use, modification, and in-hospital death in patients with COVID-19: A cohort study.

AIMS: To assess the associations of exposure and modifications in exposure (i.e., discontinuation on admission, initiation during hospitalization) to eight common cardiovascular therapies with the risk of in-hospital death among inpatients with coronavirus disease 2019 (COVID-19). METHODS: In this observational study including 838 hospitalized unvaccinated adult patients with confirmed COVID-19, the use of cardiovascular therapies was assessed using logistic regression models adjusted for potential confounders. RESULTS: No cardiovascular therapy used before hospitalization was associated with an increased risk of in-hospital death. During hospitalization, the use of diuretics (aOR 2.59 [1.68-3.98]) was associated with an increase, and the use of agents acting on the renin-angiotensin system (aOR 0.39 [0.23-0.64]) and lipid-lowering agents (aOR 0.41 [0.24-0.68]) was associated with a reduction in the odds of in-hospital death. Exposure modifications associated with decreased survival were the discontinuation of an agent acting on the renin-angiotensin system (aOR 4.42 [2.08-9.37]), a ß-blocker (aOR 5.44 [1.16-25.46]), a lipid-modifying agent (aOR 3.26 [1.42-7.50]) or an anticoagulant (aOR 5.85 [1.25-27.27]), as well as the initiation of a diuretic (aOR 5.19 [2.98-9.03]) or an antiarrhythmic (aOR 6.62 [2.07-21.15]). Exposure modification associated with improved survival was the initiation of an agent acting on the renin-angiotensin system (aOR 0.17 [0.03-0.82]). CONCLUSION: In hospitalized and unvaccinated patients with COVID-19, there was no detrimental association of the prehospital use of any regular cardiovascular medication with in-hospital death, and these therapies should be continued as recommended.

Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode.

AIM OF THE STUDY: Patients surviving COVID-19 have been described as being at risk of developing sequelae. We aimed to investigate and elicit persistent symptoms, emotional status and quality-of-life in patients discharged after an acute COVID-19 episode. METHODS: Patient-reported outcome measures were collected during a telephone interview 30 days and 1 year after discharge. Patients' general health status was evaluated using questions based on their symptoms, emotional status was assessed using the items 9 to 12 of the HeartQoL questionnaire and quality of life was assessed at 1 year through the EQ-5D-5L. In patients with a history of cardiovascular disease, all 14 items of the HeartQoL questionnaire were completed to derive the HeartQoL global score. RESULTS: Among 687 patients who survived after being hospitalised for COVID-19 at the University Hospitals of Geneva between 26 February and 26 April 2020, 184 (27%) and 165 (24%), respectively, participated in the follow-up at 30 days and 1 year. Of these 184 participants, 62% were male, median age was 58 years and 21% had a past medical history of cardiovascular disease. At one month after discharge, 61% (113/184) of patients presented fatigue and 28% (52/184) dyspnoea. One year after discharge, the main complaints were persistent fatigue in 27% (45/165) of patients, neurological problems in 17% (28/165) and dyspnoea in 14% (23/165). Eight percent (14/184) of patients declared being significantly worried 1 month after discharge and 5% (9/184) feeling depressed. The number of patients reporting being significantly worried or depressed at 1 year was lower. Regarding the quality of life at 1 year, the median EQ-5D-5L visual analogue scale score was 80 (interquartile range 70-90). CONCLUSIONS: Approximately half of patients reported some symptoms 1 year after discharge following an acute episode of COVID-19. The predominant symptom was persistent fatigue both at 1-month and at 1-year follow-up. Emotional status and quality of life appeared satisfactory.

[Janus kinase inhibitors : new perspectives for precision medicine ?] / Inhibiteurs des Janus kinases : nouvelles perspectives pour la médecine de précision ?

Janus kinase inhibitors (JAKi), such as tofacitinib, baricitinib, upadacitinib or ruxolitinib, are small molecules active on specific intracellular targets and used orally for the treatment of autoimmune or myeloproliferative diseases. Their remarkable therapeutic efficacy is offset by a significant risk of toxicities, essentially dose-dependent and a variable pharmacokinetic profile. The JAKi represent a new therapeutic armamentarium for treating autoimmune, myeloproliferative and inflammatory diseases (incl. COVID-19), but require thorough treatment individualization and close monitoring. Therapeutic Drug Monitoring (TDM) of JAKi could allow a personalized prescription and improve the efficacy-toxicity profile.

Les inhibiteurs des Janus kinases (JAKi), tels que le tofacitinib, le baricitinib, l'upadacitinib ou le ruxolitinib, représentent une nouvelle classe de petites molécules actives sur des cibles intra-cellulaires spécifiques, utilisables par voie orale pour traiter des maladies autoimmunes ou néoplasies myéloprolifératives. Leur efficacité thérapeutique remarquable est contrebalancée par un risque significatif de toxicités essentiellement dose-dépendantes et un profil pharmacocinétique variable. Les JAKi constituent une nouvelle arme thérapeutique pour le traitement des maladies autoimmunes, myéloprolifératives et inflammatoires (Covid-19), mais nécessitent une individualisation et un suivi attentifs. Le suivi thérapeutique des médicaments des JAKi pourrait permettre de personnaliser leur prescription et améliorer leur profil efficacité-toxicité.

Multifocal lymphadenopathies with polyclonal reactions primed after EBV infection in a mRNA-1273 vaccine recipient.

We report a case of recurrent tender, multifocal lymphadenopathies associated with B-symptoms, clinically mimicking lymphoma in a mRNA-1273 vaccine recipient after a recent Epstein-Barr virus (EBV) infection. In the lymph node biopsy, monocytoid B-cell hyperplasia, TH2 (GATA3+) predominance, and hyperplasia of interferon-gamma-producing plasmacytoid dendritic cells were observed along with sustained neutralising antibody production against SARS-CoV-2 wild-type and five variants. High titres of anti-S antibodies and neutralising antibodies were observed, excepted for variant B.1.529** (omicron) and B.1.351** (beta), due to several mutations in the spike protein, including the E484K mutation. We postulated that EBV acted as an immunological enhancer with the mRNA-1273 vaccine, inducing a sustained inflammatory response over several weeks. However, the polyclonal nature of the lymphadenopathy with polytypic plasmacytosis and pseudo-tumoural reaction cell hyperplasia were associated with failure to mount acute phase responses.

Mortality and high risk of major adverse events in patients with COVID-19 and history of cardiovascular disease.

OBJECTIVE: History of cardiovascular diseases (CVDs) may influence the prognosis of patients hospitalised for COVID-19. We investigated whether patients with previous CVD have increased risk of death and major adverse cardiovascular event (MACE) when hospitalised for COVID-19. METHODS: We included 839 patients with COVID-19 hospitalised at the University Hospitals of Geneva. Demographic characteristics, medical history, laboratory values, ECG at admission and medications at admission were collected based on electronic medical records. The primary outcome was a composite of in-hospital mortality or MACE. RESULTS: Median age was 67 years, 453 (54%) were males and 277 (33%) had history of CVD. In total, 152 (18%) died and 687 (82%) were discharged, including 72 (9%) who survived a MACE. Patients with previous CVD were more at risk of composite outcomes 141/277 (51%) compared with those without CVD 83/562 (15%) (OR=6.0 (95% CI 4.3 to 8.4), p<0.001). Multivariate analyses showed that history of CVD remained an independent risk factor of in-hospital death or MACE (OR=2.4; (95% CI 1.6 to 3.5)), as did age (OR for a 10-year increase=2.2 (95% CI 1.9 to 2.6)), male gender (OR=1.6 (95% CI 1.1 to 2.3)), chronic obstructive pulmonary disease (OR=2.1 (95% CI 1.0 to 4.2)) and lung infiltration associated with COVID-19 at CT scan (OR=1.9 (95% CI 1.2 to 3.0)). History of CVD (OR=2.9 (95% CI 1.7 to 5)), age (OR=2.5 (95% CI 2.0 to 3.2)), male gender (OR=1.6 (95% CI 0.98 to 2.6)) and elevated C reactive protein (CRP) levels on admission (OR for a 10 mg/L increase=1.1 (95% CI 1.1 to 1.2)) were independent risk factors for mortality. CONCLUSION: History of CVD is associated with higher in-hospital mortality and MACE in hospitalised patients with COVID-19. Other factors associated with higher in-hospital mortality are older age, male sex and elevated CRP on admission.